The principle objective is to elucidate the mechanism of drug- induced supersensitivity of the cardiovascular system. We will use a model reserpine-induced supersensitivity of rabbit aortic strips and then study the possible extension of this to supersensitivity induced by other agents in several tissues and species. We will study the possible intracellular or membrane bound calcium involvement by tension decline studies and by studying 45 calcium fluxes in whole aorta and in subcellular fractions (mitochondria microsomes). After we have defined the gross and subcellular characteristics of reserpine-induced supersensitivity, we will study that induced by guanethidine, alpha- methyl dopa and 6-OH-dopamine.